Device for intravascular delivery of beta emitting isotopes

ABSTRACT

The present invention provides a device ( 10 ), and methods of use thereof, for the targeted delivery of radiation, in vivo. The therapeutic radiation delivered by the device ( 10 ) of the present invention can be used, for example, to prevent restenosis after angioplasty. The catheter device ( 10 ) of the present invention is especially suited for such treatment because it substantially aids in the delivery of radiation to an intravascular treatment site. In addition, to delivering radiation emitting materials to an intravascular site, the present invention can also incorporate radiation shielding to increase the safety and accuracy of the delivery of the radiation emitting materials.

This patent application claims priority from U.S. ProvisionalApplication No. 60/064,611, filed Nov. 7, 1997; U.S. ProvisionalApplication No. 60/080,052, filed Mar. 31, 1998; and U.S. ProvisionalApplication No. 60/087,202, filed May 29, 1998.

FIELD OF THE INVENTION

The present invention relates to catheters designed for delivery oftherapeutic substances in vivo. More specifically, the present inventionrelates to catheters designed for intravascular delivery of therapeuticradiation in vivo.

BACKGROUND OF THE INVENTION

Isotopic radiation therapy has been proposed for the treatment ofvarious vascular disorders, such as restenosis following angioplasty.Prior to the present invention, it was believed that gamma emittingisotopes would be useful for peripheral brachy therapy. However, the useof gamma emitting isotopes poses a great deal of logistical difficultyin safely delivering the isotope.

The use of beta emitting isotopes would be easier and safer for vascularbrachy therapy because beta emitting isotopes have relatively lowpenetrance and are easier to shield. However, the use of beta emittingisotopes is limited by the penetrating depth, which is about 3-4 mm atthe appropriate doses required for intervention. Many arteries arelarger than 3-4 mm, for example measuring 5 to 7 mm in diameter in thesuperficial femoral artery and even larger in the aortoiliac system.

What is needed is a device for intravascular delivery which allows forthe use of radiation emitting isotopes in larger diameter vessels, andwhich minimizes the safety precautions required by gamma emittingisotopes.

SUMMARY OF THE INVENTION

The present invention provides a device, and methods of use thereof, forthe targeted delivery of radiation in vivo. The therapeutic radiationdelivered by the device of the present invention can be used, forexample, to prevent restenosis after angioplasty. The catheter of thepresent invention is especially suited for such treatment because itsubstantially aids in the delivery of radiation to an intravasculartreatment site.

Further, the device of the present invention makes it possible for betaemitting isotopes to be used as sources of therapeutic radiation. Theuse of beta emitting isotopes is advantageous because they have lowpenetrance, e.g., in the range of 3-4 mm, and they are relatively easyto shield. Prior to the present invention, the low penetrance of thebeta emitting isotopes has limited their usefulness in treating vascularsites because many vascular sites exceed in size the penetrance of betaemitting isotopes. By using the beta emitting isotopes in conjunctionwith the catheter of the present invention, this problem can be overcomeby placing the beta emitting isotope at the vascular site. The presentinvention further overcomes this problem by placing the beta emittingisotopes in channels located on the periphery of an inflatable balloonconnected to the end of the catheter. This balloon also increases theaccuracy of the treatment delivery by immobilizing the catheter tip atthe treatment site.

The present invention can also provide greater control over radiationdelivery by providing a return channel for the radiation emittingisotopes rather than merely a blind port. Such a return channel allowsfor greater control of the treatment duration, as well as greaterflexibility in dosing regimens. Further, the path of such returnchannels can also contribute to the radiation delivery.

The present invention allows delivery of isotopes via several methods.These include, but are not limited to, radioactive wires, radioactiveseed trains, radioactive gases and liquids, as well as other radiationemitting materials known to one skilled in the art. Preferably, thepresent invention utilizes beta emitting isotopes, but other types ofradiation emitting materials may be used and is contemplated as withinthe scope of the present invention. Examples of beta emitting isotopesused with the present invention are ⁹⁰strontium, ¹²⁵iodine, ¹⁹²iridium,itrium, ¹⁸⁸rhenium, ¹⁸⁶rhenium and ¹³³xenom.

In another embodiment of the present invention, the catheter can alsoinclude a radiation shielding. Such shielding is used to increase theaccuracy and safety of the radiation delivery by preventing undesiredradiation emission from the delivery channels. Further, radiationshielding can be used in the present invention to avoid the necessity ofcomplex afterflow devices. For example, radiation emitting isotopes canbe situated within radiation shielding inside the catheter. Once thecatheter is in place, the radiation emitting isotopes can be exposed.This can be accomplished, alternatively, by moving the shielding or bymoving the radiation emitting isotopes, such that the radiation emittingisotopes are no longer shielded.

The present invention can also take the form of a double cathetersystem. In this embodiment of the present invention, the inner, shieldedcatheter contains a movable radiation emitting source. The radiationemitting source can be, for example, an irradiated wire or a series ofradiation emitting pellets embedded in a plastic wire matrix. The wirecan be movable such that it can be extended beyond the distal end of theradiation shielding. The present invention also provides that thisshielded catheter can have a radiation proof valve located on its distaltip. An outer catheter can contain two lumens: an eccentrically locatedguide wire lumen and a large lumen sized to receive the inner, shieldedcatheter. The shielded catheter can be inserted into the outer catheterprior to insertion of the catheter system in vivo. Once the catheter hasbeen properly placed in vivo, the radiation emitting wire can beextended beyond the shielding to complete the delivery of the radiationto the treatment site.

Such a system can provide a number of advantages. For example, the outercatheter can be disposable. Additionally, the shielded catheter can beused to store the radiation emitting source between uses. Such a systemalso avoids the necessity of complex afterflow devices.

The present invention can also comprise a method of delivering radiationto an in vivo treatment site using a catheter. This method can comprisethe steps of inserting the catheter until it is properly positioned invivo; delivering the radiation emitting isotopes through the catheter orunshielding the radiation emitting source within the catheter; allowingthe radiation treatment to continue for the appropriate amount of time;and then removing and/or reshielding the radiation emitting source.

Accordingly, it is an object of the present invention to providecatheters and methods that can safely and accurately deliver radiationemitting substances to a desired site.

It is another object of the present invention to provide catheters andmethods that can safely and accurately deliver beta radiation emittingisotopes to a desired site.

It is another object of the present invention to provide a catheter andmethod that can be used to locally treat a diseased area usingradiation.

It is another object of the present invention to provide a catheter andmethod that can be used to treat an intravascular site using radiation.

It is another object of the present invention to provide a catheter andmethod that can be used to treat restenosis.

It is another object of the present invention to provide a catheter andmethod that can be used to increase the therapeutic effectiveness ofbeta emitting isotopes by delivering them such that the distance betweenthe beta emitting isotopes and the treatment site is less than thepenetrance of the beta emitting isotopes.

It is another object of the present invention to provide a catheter andmethod that can be used to increase the effectiveness and safety ofradiation therapy by utilizing radiation shielding.

These and other objects, features and advantages of the presentinvention will become apparent after a review of the following detaileddescription of the disclosed embodiments and the appended claims.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 shows an embodiment of a device for the delivery of radiationemitting isotopes of the present invention.

FIG. 2 shows an embodiment of a device for the delivery of radiationemitting isotopes including a centrally-located return channel.

FIG. 3 shows an embodiment of a device for the delivery of radiationemitting isotopes including a return channel configured in a reverseparallel spiral relative to the peripheral coil.

FIG. 4 shows an embodiment of a device for the delivery of radiationemitting isotopes including a return channel configured in a reversehelical design relative to the peripheral coil.

FIG. 5 shows a catheter with a lumen capable of receiving a shieldingcatheter for use with the double catheter embodiment of the presentinvention.

FIG. 6 shows an embodiment of a shielding catheter with an activeisotope wire extended for use with the double catheter embodiment of thepresent invention.

FIG. 7 shows an embodiment of a series of radiation emitting pelletsembedded in a plastic wire matrix for use in a shielding catheter of thedouble catheter embodiment of the present invention.

FIG. 8 shows a double catheter embodiment with a shielding cathetersecured by a locking mechanism within an outer catheter with anirradiated wire extended from the shielding catheter.

FIG. 9 shows a double catheter embodiment with a shielding cathetersecured by a locking mechanism within an outer catheter with anirradiated wire contained within the shielding catheter.

FIG. 10 shows an embodiment of a shielding catheter having a lockingmechanism to prevent the accidental depression of the syringe mechanismand having a radiation proof valve.

DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

The present invention provides a device, and methods of use thereof, forthe targeted delivery of radiation in vivo. The therapeutic radiationdelivered by the device of the present invention can be used, forexample, to prevent restenosis after angioplasty. The catheter of thepresent invention is especially suited for such treatment because itsubstantially aids in the delivery of radiation to an intravasculartreatment site.

As shown in FIG. 1, the present invention can be embodied in a device10, and methods of use thereof, for the intravascular delivery ofradiation emitting isotopes. Beta emitting isotopes are preferred,however, any radiation emitting isotope can be used in the presentinvention. Uses of the device are not limited to any particular physicalform of radioactive isotope, i.e. whether solid, liquid or gaseous. Thedevice 10 has a proximal end 12 and a distal end 14. The device 10comprises a central wire 16 containing lumen 20 used to direct thedistal end 14 into position within a vascular cavity, e.g. an artery.The wire 16 can be left in place during operation, or removed, as theisotope is delivered peripherally as described below.

A central balloon 30 is inflated via an inflator channel 35 to securethe device 10 into position within the vascular cavity. A peripheralcoil 40 is supplied with a therapeutic radiation emitting isotope via adelivery channel 45. The peripheral coil 40 is a stiff walled,closed-end channel wrapping the central balloon 30 in successive coils.In preferred embodiments, the balloon 30 can be about 10 mm with eachloop of the peripheral coil 40 spaced about 1-2 mm apart. The isotope isdelivered to the delivery channel 45 via an afterloader and sent intothe vessel within the peripheral coil 40 surrounding the central balloon30. After treatment, the isotope is retracted, the central balloon 30 isdeflated and the device 10 is withdrawn from the vascular cavity.

FIG. 2 shows another embodiment of the present invention. The peripheralcoil 40 does not terminate in a “blind port” fashion, but instead isprovided with a return lumen 50. This modification makes the deliverylumen “circular” in design. The return lumen 50 runs centrally as shownin FIG. 2, or, as shown in FIG. 3, can be configured in a reverseparallel spiral or, as shown in FIG. 4, can be configured in a reversehelical design. These embodiments allow a continuous loop for deliveryof a liquid or gaseous substance, entering through one inflow deliverychannel 45 and circling the balloon 30 with exit through the returnlumen 50. The balloon design and central wire lumen design can be thesame or different as in the first embodiment.

The present invention also contemplates that catheters containingoptical fibers can be used for the delivery of electromagnetic radiationenergy to the vessel walls. For example, the peripheral coil 40 can besupplied with such an optical fiber or bundle of fibers to emittherapeutic radiation via the delivery channel 45.

Furthermore, the present invention contemplates that catheters capableof emitting an electrical discharge can be used in conjunction with thedevice 10 for the therapeutic modulation of cell membranes. For example,the peripheral coil 40 and delivery channel 45 can be supplied with suchan electrical catheter to emit therapeutic electrostimulation to thevascular cavity via the delivery channel 45. Alternatively, a separatelumen containing an electrical stimulator can be wrapped around thecentral balloon 30 in a parallel spiral with the peripheral coil 40, andthereby electrical charges can be administered to the vascular cavityalong with the above-described isotopic or electromagnetic irradiation.

Further embodiments of the present invention also include radiationshielding to reduce unwanted irradiation. Embodiments includingradiation shielding function to target radiation delivery by themanipulation of the relative positions of the radiation emittingmaterials and the radiation shielding. For example, a shielded radiationemitting material can be delivered to a desired location in vivo. Then,to effectuate delivery of radiation, the positions of the radiationemitting materials and the radiation shielding relative to each othercan be altered such that the radiation emitting material is no longershielded. The radiation shielding can be withdrawn, thereby unshieldingthe radiation emitting material; or, the radiation emitting material canbe extended within the catheter beyond the radiation shielding.

The radiation shielding can be lead or one of several other materialssuch as various heavy metals. Other examples of radiation shieldingmaterial used in the present invention include tin, heavy plastic orother soft metals. Additionally, some of the embodiments of the presentinvention include radiation shielding in the form of a spiral coil inorder to increase the flexibility of the radiation shielding. The choiceof which material to use depends upon various factors such as thickness,cost, and flexibility and will vary depending upon the particularapplication, which is routinely determinable to one skilled in the art.

Such embodiments can further contain radiation proof valves. On thedistal ends of the radiation shielded portions, such valves would reduceunwanted irradiation both prior to and after the catheter being placedin vivo. These valves provide radiation shielding while still allowingthe radiation emitting material to selectively pass through them in bothdirections.

The movement of the radiation emitting material and/or the radiationshielding is achieved through various mechanisms. For example, amanually operated syringe mechanism can be used. In such a mechanism, aplunger is connected to the proximal end of the portion of the system tobe moved, e.g. the radiation emitting material.

A preferred embodiment utilizing radiation shielding is shown in FIGS.5-10. The radiation delivery system 100 is a two-part catheter system.The first part is a double lumen catheter 110. The larger central lumen112 has an open proximal end 114 and a closed distal end 116. A secondlumen 118 is eccentrically located and acts as the guide wire lumen. Thesystem allows for the retraction of the wire from the delivery areaafter positioning of the catheter system 100. The second part of thedelivery system 100 is a shielding catheter 130. The shielding catheter130 houses the active isotope, for example, in the form of a wire 132.The active isotope wire 132 is a radiation emitting wire, as shown inFIG. 6, or a series of radiation emitting pellets embedded in a plasticwire matrix 134, as shown in FIG. 7. The wire 132 is slidably attachedwithin the lumen 136 of the shielding catheter 130 such that the wire132 may slide in and out of the distal end of the shielding catheter130. The shielding catheter 130 is constructed of such a shieldingmaterial 138 as to shield any radiation emissions while the activeisotope wire 132 is contained within the shielding catheter 130. Asyringe mechanism 140 is located at the proximal end of the shieldingcatheter 130 and has a movable plunger 142 that is connected to theproximal end of the active isotope wire 132. When the plunger 142 iswithdrawn, the active isotope wire 132 is housed completely within theshielding catheter 130, as shown in FIG. 9. When the plunger 142 isdepressed, the wire 132 extends from the distal end of the shieldingcatheter 130, as shown in FIG. 8. The distal end of the shieldingcatheter 130 is closed by a radiation proof valve 150. The radiationproof valve 150 acts to prevent any radiation leak out of the distal endof the shielding catheter 130 while still allowing the active isotopewire 132 to be moved in and out of the shielding catheter 130.

The large central lumen 112 of the double lumen catheter 110 is sized toreceive the shielding catheter 130 within it. A locking mechanism 160can also be provided to secure the shielding catheter 130 within thedouble lumen catheter 110 once the shielding catheter 130 has been fullyinserted. A locking mechanism 170 can also be provided on the syringemechanism 140 of the shielding catheter 130 to prevent accidentalextension of the active isotope wire 132. Raised shoulders 180 can alsobe provided within the large central lumen 112 of the double lumencatheter 110. These shoulders 180 can act as brakes aiding in the fulland proper insertion of the shielding catheter 130, as shown in FIG. 8.These shoulders 180 can be composed of a visualizable material, such asa radio opaque material, to aid in the proper positioning and targetingof the catheter system 100 and thereby aid in the targeting of theradiation delivery.

The outer double lumen catheter 110 can be disposable and designed for asingle use only. The shielding catheter 130 can be used multiple timesand can act as a storage container for the active isotope wire 132between uses.

The present invention can also comprise a method of delivering radiationto an in vivo treatment site using a catheter. This embodiment of thepresent invention comprises the steps of inserting the catheter into thedesired part of the body until it is properly positioned in vivo;delivering the radiation emitting isotopes through the catheter orunshielding the radiation emitting source within the catheter; allowingthe radiation treatment to continue for the appropriate amount of time;and then removing and/or reshielding the radiation emitting source. Thetreatment time and frequency can easily be varied. The preferredfrequency is a single treatment. The treatment time can be up to 30 to40 minutes or even greater. Preferably, the treatment time isapproximately 3-4 minutes. Placement of the radiation emitting materialwithin the intravascular site can reduce the treatment time needed.Further, the placement of beta emitting isotopes closer to the vascularwalls by delivering the isotopes through a peripheral coil wrappedaround the inflatable balloon can reduce the treatment time needed andincrease the effectiveness of the radiation treatment.

It should be understood, of course, that the foregoing relates only topreferred embodiments of the present invention and that numerousmodifications or alterations may be made therein without departing fromthe spirit and the scope of the present invention as set forth in theappended claims.

What is claimed is:
 1. A device for delivering radiation to an in vivotreatment site comprising: an inner shielding catheter comprising aradiation shielded lumen and a radiation emitting portion comprising aradiation emitting material movable within the shielded lumen of theshielding catheter, wherein the radiation emitting material is axiallyslidable between a first configuration in which the radiation emittingmaterial is contained within the shielded lumen and a secondconfiguration in which the radiation emitting material extends from thedistal end of the shielding catheter; an outer catheter comprising atleast a first lumen and a second lumen, wherein the first lumen is sizedto receive the shielding catheter and the second lumen is capable ofreceiving a guide wire; and a radiation proof valve on the distal end ofthe shielded lumen.
 2. The device of claim 1, wherein the radiationemitting material is a beta emitting isotope.
 3. The device of claim 1,wherein the in vivo treatment site is an intravascular site.
 4. Thedevice of claim 1, wherein the outer catheter is disposable.
 5. A devicefor delivering radiation to an in vivo treatment site comprising: aninner shielding catheter comprising a radiation shielded lumen and aradiation emitting portion comprising a radiation emitting materialmovable within the shielded lumen of the shielding catheter, wherein theradiation emitting material is axially slidable between a firstconfiguration in which the radiation emitting material is containedwithin the shielded lumen and a second configuration in which theradiation emitting material extends from the distal end of the shieldingcatheter; an outer catheter comprising at least a first lumen and asecond lumen, wherein the first lumen is sized to receive the shieldingcatheter and the second lumen is capable of receiving a guide wire; anda locking mechanism capable of selectively securing the shieldingcatheter within the outer catheter.
 6. The device of claim 5, whereinthe radiation emitting material is a beta emitting isotope.
 7. Thedevice of claim 5, wherein the in vivo treatment site is anintravascular site.
 8. The device of claim 5, wherein the outer catheteris disposable.
 9. A device for delivering radiation to an in vivotreatment site comprising: an inner shielding catheter comprising aradiation shielded lumen and a radiation emitting portion comprising aradiation emitting material movable within the shielded lumen of theshielding catheter, wherein the radiation emitting material is axiallyslidable between a first configuration in which the radiation emittingmaterial is contained within the shielded lumen and a secondconfiguration in which the radiation emitting material extends from thedistal end of the shielding catheter; an outer catheter comprising atleast a first lumen and a second lumen, wherein the first lumen is sizedto receive the shielding catheter and the second lumen is capable ofreceiving a guide wire; and a locking mechanism capable of selectivelypreventing movement of the radiation emitting material.
 10. The deviceof claim 9, wherein the radiation emitting material is a beta emittingisotope.
 11. The device of claim 9, wherein the in vivo treatment siteis an intravascular site.
 12. The device of claim 9, wherein the outercatheter is disposable.
 13. A device for delivering radiation to an invivo treatment site comprising: an inner shielding catheter comprising aradiation shielded lumen and a radiation emitting portion comprising aradiation emitting material movable within the shielded lumen of theshielding catheter, wherein the radiation emitting material is axiallyslidable between a first configuration in which the radiation emittingmaterial is contained within the shielded lumen and a secondconfiguration in which the radiation emitting material extends from thedistal end of the shielding catheter; an outer catheter comprising atleast a first lumen and a second lumen, wherein the first lumen is sizedto receive the shielding catheter and the second lumen is capable ofreceiving a guide wire; and a shoulder at the distal end of the outercatheter capable of stopping the insertion of the shielding catheter.14. The device of claim 13, wherein the shoulders are observable invivo.
 15. A device for delivering radiation to an in vivo treatment sitecomprising a catheter having a proximal end and a distal end, furthercomprising: a lumen for receiving a guidewire; an inflatable balloon onthe distal end of the catheter capable of immobilizing the distal end ofthe catheter at the treatment site when inflated; an inflator channel incommunication with the inflatable balloon; and a radiation channelcapable of delivering a radiation emitting material to the treatmentsite without releasing the radiation emitting material from thecatheter, wherein the radiation channel is peripherally wound around theinflatable balloon.
 16. The device of claim 15, wherein the radiationemitting material is a beta emitting isotope.
 17. The device of claim15, wherein the in vivo treatment site is an intravascular site.
 18. Adevice for delivering radiation to an in vivo treatment site comprisinga catheter having a proximal end and a distal end, further comprising: alumen for receiving a guidewire; an inflatable balloon on the distal endof the catheter capable of immobilizing the distal end of the catheterat the treatment site when inflated; an inflator channel incommunication with the inflatable balloon; a radiation channel capableof delivering a radiation emitting material to the treatment sitewithout releasing the radiation emitting material from the catheter, anda return flow channel in communication with the radiation channel. 19.The device of claim 18, wherein the radiation emitting material is abeta emitting isotope.
 20. The device of claim 18, wherein the in vivotreatment site is an intravascular site.